Crystallization of alpha monosodium citrate monohydrate

ABSTRACT

Monosodium citrate monohydrate crystals are prepared by evaporating an aqueous solution containing monosodium citrate whilst maintaining said solution between 20*C and 60*C and at a concentration of monosodium citrate of not less than 155 % (W/V) of saturation solubility of gamma -crystals of monosodium citrate. Thus obtained crystals have a good filtrability and separability from a solution and are widely applicable as foods, pharmaceuticals and chemical products.

United States Patent [1 1 Nara et al.

[ CRYSTALLIZATION OF ALPHA MONOSODIUM CITRATE MONOHYDRATE [75]Inventors: Kiyoshi Nara, Kyoto; Kazuyoshi Katamoto, Osaka; KazuhikoOhta, Osaka; Hideo Fukuda, Osaka, all of Japan [73] Assignee: TakedaChemical Industries, Ltd.,

Japan 22 Filed: Apr. 25, 1974 [2i] Appl.No.:464,6l4

[ Dec. 9, 1975 1,57l,55l 5/1969 France r r i i 260/535 P l,596,0567/1970 France r t w .7 260/535 P 20,395 6/1972 Japan 260/535 P OTHERPUBLICATIONS Burns, D. M. et al., Acta Crystallographica, Vol 7, pp.137-l38, i954.

Groth, P. Chemische Krystallographic, Vol. III, pp. 465 and 477.

Primary Examiner-James A. Patten Assistant Examiner-Killos Attorney,Agent, or FirmWenderoth, Lind & Ponack [57] ABSTRACT Monosodium citratemonohydrate crystals are prepared by evaporating an aqueous solutioncontaining monosodium citrate whilst maintaining said solution between20C and 60C and at a concentration of monosodium citrate of not lessthan I55 (W/V) of saturation solubility of y-crystals of monosodiumcitrate. Thus obtained crystals have a good filtrability andseparability from a solution and are widely applicable as foods,pharmaceuticals and chemical prodnets.

4 Claims, 5 Drawing Figures U.S. Patent Dec. 9, 1975 Sheet 1 of23,925,465

FIG. I

FIG. 3 FIG. 4

U.S. Patent Dec. 9, 1975 Crystallization Velocity of Monosodium CitrateSheet 2 of 2 FIG. 5

O0 Maximum Allowable Crystallization Velocity 4 x------x Opperated.Crystallization Velocity O l I l l I Time (H CRYSTALLIZATION OF ALPHAMONOSODIUM CITRATE MONOHYDRATE This invention relates to large-sizedcrystals of monosodium citrate monohydrate and preparation thereof froman aqueous solution containing monosodium citrate, said crystals beingseparable with efficiency from the solution.

Monosodium citrate is a compound which, either as it is or in the formof free citric acid, finds application in the fields of foodstuffs,pharmaceuticals and chemical products. Though a method for producingcitric acid by means of yeasts has recently been developed (e.g. FrenchPat. Nos. 1,571,551, 1,596,056 and 7,002,162), the method inevitablygives rise to some amounts of isocitric acid and other organic acids ascontaminants even if cultural conditions and other factors are carefullycontrolled. Several attempts have been made to recover monosodiumcitrate or citric acid from such solutions containing isocitric acid andother impurities. One of the proposed procedures comprises, as it is thecase with the conventional treatment of culture broths of filamentousfungi, converting the citric acid in the broth to calcium citrate,adding sulfuric acid so as to decompose the calcium citrate to citricacid and calcium sulfate, concentrating this citric acid solution tocause the citric acid to separate as crystals and recovering thecrystals from the solution (Japanese Pat. Publication No. 20395/1972).

Another method comprises adding sodium hydroxide, for instance, to theculture broth, concentrating the broth to let trisodium citrate separateas crystal, collecting the crystals, subjecting them to an ion exchangetreatment or electrodialysis, for instance, to remove the sodium andharvesting the resultant citric acid.

However, the method involving the intermediate formation of calciumcitrate has not a few disadvantages, among which are the difficultiesincidental to the handling and treatment of solids such as calciumcitrate and byproduct calcium sulfate. The method via trisodium citratealso has many disadvantages. For example, the method of necessityinvolves the addition of a large amount of sodium to the culture brothand, to remove the sodium, fairly large-scale equipment is required.

In view of the foregoing disadvantages of prior art, the presentinventors made an extensive study to develop a commercially advantageousmethod of recovering monosodium citrate from a fermentation broth, whichmethod should require addition of only a minimum amount of sodium to thebroth and, accordingly, should enable us to separate and recover thedesired product in the form of monosodium citrate which is comparativelyready to release the sodium. Thus, for example, the present inventorstentatively adjusted a fermentation broth containing both citric acidor/and isocitric acid to pH about 3.0 4.0 with an acid such ashydrochloric acid or sulfuric acid or with an alkali such as sodiumhydroxide or sodium carbonate, separated the cells from the broth andconcentrated the filtrate in the routine manner to cause crystals ofcitric acid to separate. In so doing, the present inventors discoveredthat depending upon the concentration temperature employed, at leastfour different types of crystals are produced. By way of example, if anaqueous solution of monosodium citrate is concentrated and crystallizedat 65C, there will be obtained small anhydrous 2 hexagonal platelets(hereafter called 'y-crystals). At 55C, the formation of 'y-crystals isaccompanied by the separation of large hexagonal plates (hereaftercalled B-crystals) and large prisms (hereafter called oz-crystals). Boththe aand B-crystals are monosodium citrate monohydrate.

When a similar aqueous solution of monosodium citrate is concentrated at40C and rapidly cooled to 10C 20C, small anhydrous cubic crystals(hereafter called B-crystals) separate. These different crystals areshown in FIGS. 1 to 4. Thus, FIGS. 1, 2, 3 and 4 are microphotographsshowing the 01-, 3-, yand fi-crystals, respectively. The microphotographof FIG. 1 is of 30 times magnification, and the microphotographs ofFIGS. 2, 3 and 4 are of 60 times magnification.) These crystals havefollowing unique X-ray diffraction characteristics at \=l.542 A (Cu K-line, 40 KV, mA, Ni-filter).

(ax-crystals) (Bcrystals) Spacing dA Relative Spacing dA Relativeintensities intensities 7.8 s 7.0 s 6.4 m 5.9 vw 5.4 m 5.4 vw 4.1 w 5.3w 4.0 w 5.2 m 3.89 vs 4.5 vw 3.79 vw 4.3 w 3.71 m 4.2 w 3.58 w 3.66 w3.49 m 3.54 m 3.35 w 3.42 w 3.30 w 3.13 w 3.25 vw 3.10 vw 3.18 m 3.04 m2.92 w 2.97 vw 2.77 vw 2.93 w 2.70 w 2.88 w 2.60 w 2.71 w 2.55 w 2.64 w2.45 vw 2.30 w 2.42 m 2.36 vw 2.34 w 2.29 w

(qr-crystals) (B-crystals) Spacing (1 Relative Spacing d Relativeintensities intensities 6.8 vw b 7.3 vs 5.1 m 5.8 m 4.2 w 5.0 m 3.87 m4.7 m 3.74 vw 4.6 m 3.6l vw 4.4 vw 3.46 m 3.65 m 3.36 m 3.60 m 3.10 w3.55 m 2.94 vw 3.46 w 2.87 vw 3.38 w 2.73 vw 3.08 m 2.70 vw 2.95 vw 2.54vw 2.93 vw 2.49 w 2.80 w 2.41 m 2.71 w 2.37 vw 2.68 m 2.35 w 2.56 vw2.41 vw 2.37

Note:

vw=vcry weak. Weak m-medium. s-strong. vs=very strong. b==broad Thepresent inventors further made a research to develop a method forselective separation of a-crystals which are the easiest to separatefrom solutions and the easiest to deal with on a commercial scale of allthe above-mentioned types of crystals.

The "y-crystals of monosodium citrate are more stable than any of said01-, B- and S-crystals and, if allowed to stand as they are, the 01-, B-and 8-crystals will spontaneously convert themselves to y-crystals. Thatmeans the difficulty to isolate a-crystals alone despite the abovefinding. As it was, the present inventors discovered surprisingly thatif the crystallization is performed within the temperature range of C to60C and whilst the degree of oversaturation of the solution iscontrolled at no less than 155 percent of the saturation solubility(weight/volume) of 'y-crystals of monosodium citrate at 20 to 60C. therewill be formed crystals which are almost exclusively a-crystals. Thefact is surprising, indeed, because it is more reasonable to expect thatoversaturation is conducive to the formation of y-crystals which are themost stable of all. The above finding was followed by further research,which has resulted in this invention.

Thus, the first object of this invention is to provide crystals ofmonosodium citrate monohydrate, especially a-crysals, which is separablewith efficiency from the solution.

The second object of this invention is to provide a process forselective crystallization of monosodium cidium salt. However, as long asthere is substantially one molecular equivalent of sodium ion for everymole of citric acid, the solution can be employed as the startingmaterial according to this invention.

In the method of this invention, monosodium citrate is caused toseparate from an aqueous solution of monosodium citrate by concentratingthe solution at a temperature in the range of 20 to 60C (whilst the rateof crystallization is controlled in such a way that the concentration ofmonosodium citrate in the solution will be no less than 155 percent and,preferably 155 to 300 percent, of the saturation solubility(weight/volume) of monosodium citrate -y-crystals.

The above suitable degree of oversaturation and temperature conditionswere determined from the results of Experiment I which will be describedbelow.

EXPERIMENT 1 While an aqueous solution of monosodium citrate wasmaintained at a constant temperature, a-crystals of monosodium citratewere added as seed. Portions of the seeded solution were concentrated sothat crystals would separate at different degrees of oversaturation, andthe morphology of each of the resultant crystalline products wasinvestigated. The results are shown below.

Table 1 Relation of crystallization conditions with crystal forms ofmonosodium citrate The degree of oversaturation of monosodium citratet'y-crystals)(%) trate monohydrate. The third object is to separatecitrate from isocitrate.

Further objects of this invention will be illustrated in the followingdescription.

These objects are realized by causing monosodium citrate monohydratecrystals to separate from an aqueous solution of monosodium citrate at atemperature of 20C to 60C whilst the concentration of monosodium citrateis maintained at 155 percent of the saturation solubility(weight/volume) of monosodium citrate ycrystals at that temperature.

The starting material for the method of this invention is an aqueoussolution containing monosodium citrate. Such an aqueous solution can beobtained, for example by the following procedure. Thus, as described inFrench Pat. No. 7003025, a cellfree extract obtained from a culturebroth of a bacterium, e.g. a strain of the genus Corynebacterium, isadjusted with sodium-containing-alkali or an acid such as sulfuric acidor hydrochloric acid in such a manner that the solution will contain atleast one mole of sodium ion relative to dissolved citric acid and thepH of the solution be about 3.0 to 4.0, and, preferably, about 3.4 to3.6 (in this pH range, citrate ion and sodium alkali occur insubstantially equimolar proportions in the solution).

In the above aqueous solution, the monosodium citrate may occur eitheras it is or as dissociated into ions, or further in such forms as freeacid and, partially, diso- The relation of the degree of saturationsolubility (g/l, W/V) of monosodium citrate (y-crystals) withtemperature is shown in Table 2.

Table 2 Relation of the degree of saturation solubility (g/l, W/V) ofmonosodium citrate (y-crystals] with temperature Temperature SaturationSolubility (g/l, W/V) of (C) Monosodium Citrate (y-crystals) process,the necessary control can be obtained by adusting the concentrationvelocity. For this purpose, it is Important to monitor the concentrationof monoso- Table 3-continued Monosodium Monosodium Configuration i d'drum citrate in the solution and keep watching the mori1,' i of mmphology of the crystals being formed. 5 g/l. g/ Crystals While,normally, the crystallization temperature 2 500 25 a-crystals ought tobe as high as possible in order that the crystal- 3 500 50 and B- ylization may be performed commercially with advang 33 3 fijijfiijf tage,it is necessary that the temperature be not higher e 500 500 a andS-crystals than 60C. Over 60C, as the solution is progressively 7 500750 a'crysmls concentrated, it becomes more like slurry to rendersolid-liquid separation increasingly difficult. Particularly desirableare temperatures not exceeding 50C and not apparent the above table, thecrystal than the temperatue hreshold below which the opera configurationof monosodium citrate changes with Intion can no longer be performedcommercially with creases in the concentration of monosodium [SOCI-vantage, for example C. Irate Thus, the optimum temperature isoptionally elected However further research led the F Invenfrom betweenabout and tors to the finding that by properly controlling the crys- [nthe practice of the process of this invention, use is tanmmon P ofmonosodlum curate. accordliig 9 also made as the Starting material of anaqueous 501m 20 the concentration of co-present monosodium isocitioncontaining monosodium isocitrate besides trate, a-crystals of monosodiumcitrate can be isolated monosodium citrate, the solution beingobtainable, for P F fi from the monosodmm lsocmate' instance, bycultivating a strain of the genus Candida in comamm.g so unon'agcordance with the process as described in French The suitablecrystallization yelocity has been detertent 7,002,l62. It was found bythe present inventors in 25 mmed by the followmg Expenmem the course oftheirstudy, however, that the presence of EXPERlMENT [n monosodiumisocitrate (or lsocitnc acid) adveasely affects the formation of theobjective monosoi the concentration of monosodium, lsoc" dium citratemonohydrate crystals (wcrystals) and trate is held constant and theoversaturatlon rate of even under the afore-mentioned optimumcrystalliza- 3O "1 kept at not less than. and tion conditions forcrystallization of monosodium cithe addmon of a'crysmls of monosodium f"Hate monohydrate undesirable or s crystals are com as seed crystals,test solutions were concentrated whilst comimmly formed Thus in order)examine the inflw their temperatures were maintained at temperatures a cence of monosodium isocitrate, following Experiexceedmg C so thatmonosodium i would mem was conducted separate at various crystallizationvelocities and the configurations and separability-filtrabilitycharacteris- EXPERIMENT ll tics of the resulting crystals were studied.The results Mixtures of various proportions of monosodium are givenbelow Table 4 Crystallization velocity of g/l, monosodium Hr. citrateC0ncentta 25 200 300 400 600 tion of monosodium isocitrate incrystallization slurry 0 3". 0 0 0 0 0 0 0 0 0 5o 0 0 0 0 0 0 0 0 X 1000 o o 0 0 x x x 150 0 O 0 x x x 200 0 0 x x 250 0 x x isocitrate with asolution of monosodium citrate 55 i th table, the circle 0 denotes theemergence of Table 3 Monosodium Monosodium Configuration Experimentcitrate in isocitrate of monosodium No. solution in solution citrateg/l. crystals 1 500 0 a-crystals predominantly prism-shaped crystals(oz-crystals) of good separability and filtrability and the cross xmeans the emergence of predominantly platelets (y-crystals) or cubes of(S-crystals) of inferior separability and filtrability.

It will be seen from the above table that, even when the concentrationof monosodium isocitrate has increased, there can be obtained a-crystalsof good separability and filtrability by reducing the velocity of crys-55 tallization of monosodium citrate.

The relation of the concentration of monosodium isocitrate in thecrystallization system with the highest crystallization velocity ofmonosodium citrate which is conducive to oz-crystals is substantiallylinear as the two variables are plotted on logarithmic axes and theapproximate equation of this straight line will be:

Y= 2l9000X"- (1 wherein Y the maximum allowable crystallization velocityof monosodium citrate (g/l.Hr)

X the concentration of monosodium isocitrate in the crystallizationslurry.

Thus, in order to isolate a-crystals of monosodium citrate monohydratefrom an aqueous solution containing both monosodium citrate andmonosodium isocitrate, it is necessary, besides adhering to theforegoing crystallization conditions, to control the crystallizationvelocity of monosodium citrate (g/l.Hr) below maximum allowablecrystallization velocity Y as determined from the equation (1).

The resultant crystals of monosodium citrate monohydrate can berecovered from the aqueous solution by routine separatory proceduressuch as centrifugation or filtration.

Separability of a-crystals from the solution and their size distributionare demonstrated in the following Experiment lV.

EXPERIMENT IV Thus formed aand y-crystals are recovered as wet crystalsby glass-filtration. The amount of adherent water W/W and thedistribution of size of the crys- This result shows that a-crystals arelarger on average and more easily separable from water than 'y-crystals.

EXAMPLE 1 By the procedure described in the specification of French Pat.No. 7,003,025, Corynebacterium sp.4l6(lFO- 12729) (ATCC-21459) iscultivated at 32C for 64 hours in a 200liter fermentation tankcontaining 100 liters of a culture medium (pH 7.0) which is composed of4 of a petroleum fraction containing 92 of n-paraffins of to 12 carbonatoms, 0.2 of KH PO. 0.05 of MgSO .7H,O, 0.002 of MnSO,.7I-I O, 0.02 ofFeSO .7H O, 0.4 of Nl-l C1, 0.1 of yeast extract and 0.1 of CaCO whilethe pH of the medium is maintained at 6.5 with NaOl-l. The procedureyields 41.4 mg. of citric acid as accumulated per milliliter of theculture broth.

The broth, amounting to 100 liters, is filtered by means of a filterpress precoated with a filter aid to harvest 95 liters of a filtrate. Tothe filtrate is added Amberlite 200 C (H-form), a strongly acid cationexchange resin by Rohm and Haas Company, U.S.A., to lower the pH to 3.5.After the resin has been removed, 50 grams of activated carbon is added,followed by filtration. The carbon is washed and the washing is added tothe filtrate. Thus-obtained decolorized clear solution, amounting to 105liters (41.7 mg./ml. monosodium citrate), is concentrated at 50C andunder reduced pressure to obtain 7.5 liters of a concentrate (anoversaturated solution corresponding to I77 of 330 5 mg./ml. which isthe saturation solubility of monosodium citrate 'y-crystals at 50C).

Then, the solution is seeded with 30 grams of monosodium citratemonohydrate prisms (an-crystals) and agitated gently at a constanttemperature of 50C, whereupon oz-crystals start separating.

The crystals are examined from time to time and, as soon as evidence ofsmall hexagonal platelets, which are "y-crystals, are detected, thesystem is centrifuged to recover the crystals from the solution. Thesecrystals, weighing a total of 600 grams, are found to be a-crystals fromtheir X-ray diffraction pattern and microphotograph.

EXAMPLE 2 Using citric acid or sodium hydroxide, 4 liters of a 25.5aqueous solution of monosodium citrate is adjusted to pH 3.5.

Then, the solution is concentrated at 50C under reduced pressure to 1.72liters (an oversaturated solution corresponding to 180 of 330 mgjml.which is the saturation solubility of monosodium citrate 'y-crystals at50C). The solution is seeded with 5 grams of a-crystals of monosodiumcitrate and, while it is maintained at 50C, the system is gentlystirred, whereupon a-crystals start separating. The crystals areexamined at timed intervals and, when evidences of small hexagonalplatelets or 'y-crystals are detected, the solution is centrifuged torecover the crystals.

These crystals, weighing a total of 120 grams, are found to bea-crystals from their X-ray diffraction pattern and microphotograph.

Similarly, 4 liters of a 25.5 aqueous solution of monosodium citrate isadjusted to pH 3.5 and concentrated at 50C under reduced pressure to 2.2liters (140 oversaturation at 50C) and, then, seeded with 5 grams ofprisms (ct-crystals) of monosodium citrate monohydrate. The system isgently agitated at a constant temperature of 50C, whereupon 'y-crystalsalone separate. No a-crystals are obtained.

EXAMPLE 3 Four liters of a 25.5 aqueous solution of monosodium citrateis adjusted to pH 3.5 and concentrated at 50C under reduced pressure to2.2 liters (an oversaturated solution corresponding to 210 of 220mg./ml. which is the saturation solubility of monosodium citrate at30C). After cooling to 30C, the solution is seeded with 5 grams ofacrystals of monosodium citrate and the system is gently stirred at aconstant temperature of 30C, whereupon large prisms, which area-crystals, start separating. The crystals are observed at timedintervals and, when evidences of small hexagonal platelets, which arey-crystals, have just been detected, the system is centrifuged torecover the crystals. These crystals, weighing a total of 200 grams, arefound to be a-crystals from their X-ray diffraction pattern andmicrophotograph.

Similarly, 4 liters of a 25.5 aqueous solution of monosodium citrate isadjusted to pH 3.5 and concentrated to 1.5 liter (309 oversaturation at30C). In these instances, 8-crystals are ready to separate and, even ifa-crystals are obtained, they are extremely small-sized. On the otherhand, when the solution is concentrated only to 3.3 liters (I40 oversaturation at 30C), 'y-crystals separate.

EXAMPLE 4 To a crystallization vessel containing l liter of an aqueoussolution containing 530 g. of monosodium citrate are added 5 grams ofa-crystals of monosodium citrate as seed. While feeding the samesolution to the vessel at the rate of 800 ml./hr., the vacuumconcentration-crystallization is continued at 40-50C whilst the rate ofevaporation is controlled at 760 mls/hr.

After 1 hour, the concentration is suspended and the resultant crystalsare recovered by filtration, rinsed with a small amount of water anddried. The procedure yields 440 grams of prisms of monosodium citrate.These crystals are found to be a-crystals from their X-ray diffractionpattern and microphotograph.

EXAMPLE 5 In a culture medium containing 8 of n-hexadecane, 0.5 of (Ni-80 0.05 of MgSO .7H O, 0.025 of KH PO 50 7/l. of thiamine hydrochlorideand 0.l of antifoam, Candida lipolytica UFO-1566) (ATCC 20,324) wascultivated at 28C for 72 hours whilst the pH of the broth was maintainedat 3.5 using a solution of sodium hydroxide as a pH modifier.One-hundred liters of the cell-free broth obtained in the above manner,which contained 80 g./l. of monosodium citrate and g./l. of monosodiumisocitrate, were concentrated to obtain l. of a concentrated solution(pH 3.4) containing 533 g./l. of monosodium citrate l65 oversaturationat 45C) and 33 g./l. of monosodium isocitrate.

One liter of the concentrated solution prepared above was seeded with 5grams of prism-shaped crystals of monosodium citrate as seed crystalsand the vacuum concentration and crystallization was carried out at4050C whilst feeding the same solution to the crystallization system ata rate of 800 mljhr. and the rate of evaporation was controlled at 760ml./hr. Under the above conditions, the crystallization velocity ofmonosodium citrate was 426 g./l.-hr. The critical concentration ofmonosodium isocitrate which enabled prisms of monosodium citrate toseparate out of the solution at the above crystallization velocity was62.7 g./l. according to equation (1). Accordingly, the concentration wassuspended after l.l3 hour, by which time the concentration of monosodiumisocitrate in the crystallization mother liquor was 62.7 g./l.[(62.7-33) (33 X 0.8) l.l3]. The resultant crystals were harvested byfiltration, washed with a small amount of water and dried. The procedureyielded 500 g. of monosodium citrate prism-shaped crystals. Analysis ofthese crystals: monosodium citrate 92.0 (acrystal); monosodiumisocitrate 0.05 water 7.7

The mother liquor, whose pH was 3.2, comprised, per liter, 553 g. ofmonosodium citrate and 64 g. of monosodium isocitrate.

As a control, vacuum concentration was carried out for 1.5 hour underthe same conditions. In this case, substantial amounts of plateletsfound their way into the crop of crystals, which did not lend itselfwell to filtration. The analysis of the crystals was: 89.3 of monosodiumcitrate and L6 of monosodium isocitrate.

EXAMPLE 6 The mother liquor obtained in Example 5 (165 over-saturationrate at 45C) was decolorized by the addition of 10 g. of carbon powderand one liter portion of the solution was adjusted to pH 3.6 with anaqueous solution of sodium hydroxide. To this solution were added 5 g.of seed crystals and the vacuum evaporation and crystallization wascontinued at 40-50C whilst the same mother liquor as above wascontinuously fed to the crystallization system. The amount of feed ofmother liquor and the rate of evaporation were controlled in thefollowing manner.

Table 6 Rate of feed Rate of Crystallization Time of mother evaporationvelocity of (hour) liquor monosodium citrate 0 A 600 mL/hr. 575 ml./hr.320 g./l.-hr.

1 -2% 250 240 I33 2% 4/\ 200 I lOS The relation of the crystallizationvelocity of mono- EXAMPLE 7 To 1 l. of the mother liquor obtained inExample 6 (165 oversaturation rate at 45C) were added 5 g. of a-crystalsof monosodium citrate as seed crystals and the crystallization wascarried out gradually under cooling in such a manner that thecrystallization velocity of monosodium citrate did not exceed themaximum allowable crystallization velocity of g./l.-hr. The crystalsformed were harvested by filtration to obtain 410 g. of monosodiumcitrate prism-shaped crystals. Analysis of these crystals was: 92.l ofmonosodium citrate (oz-crystals), 0.,9 of monosodium isocitrate and 6.0of water. The mother liquor (pH 3.9) contained, per liter, 205 g. ofmonosodium citrate and M0 g. of monosodium isocitrate. The yield ofmonosodium citrate (or-crystals) from the concentrated solution to thisstage was 88.5

EXAMPLE 8 A crystallization tank was filled with 30 l. of the motherliquor obtained in the same manner as Example 5 and with the addition of50 g. of seed crystals, the vacuum evaporation and crystallization wascontinued (rate of evaporation: 16.5 l./hr.) whilst the concentratedsolution of Example 5 was fed at a rate of 30 l./hr. and the crystalslurry was withdrawn at a rate of 17 l./hr. (l2.2 l./hr. as thecrystallization mother liquor).

The crystallization velocity of monosodium citrate in this state was 330g./l.hr. and the concentration of monosodium isocitrate in the motherliquor was constant at 64 gJl. (The maximum allowable crystallizationvelocity at this concentration level of monosodium isocitrate asdetermined by equation (1) was 405 g./l.- hr.)

The vacuum evaporation and crystallization was continued for 3 hours andthe crystals that had separated out were harvested by filtration. Theprocedure yielded 31.8 kg. of prism-shaped crystals of good separabilityand filtrability.

What we claim is:

l. Prism-shaped crystals of monosodium citrate monohydrate which havethe following X-ray diffraction characteristics at )\=l.542 using a CuKline, 4O KV, 80 mA and Ni-filter:

Spacing d (A) Relative intensities Strong Medium Medium Weak Weak VeryStrong Very Weak Medium Weak Medium Weak Weak Very Weak Medium Weak VeryWeak Weak Weak Weak -contmued Spacing d (A) Relative intensities 2.45Ver Weak 2.42 Me ium 2.36 Very Weak 2'34 Weak 2.29 Weak.

2. A process for crystallization of monosodium ci- 0 trate monohydratewhich comprises subjecting to evaporation an aqueous solution containingmonosodium citrate whilst maintaining said solution at a temperaturebetween 20 and 60 Centigrade and at a concentration of monosodiumcitrate of not less than percent (weight/volume) of the saturationsolubility of ycrystals of monosodium citrate at that temperature.

3. A process for crystallization of monosodium citrate monohydrateaccording to claim 2, wherein the concentration of monosodium citrate isnot over than 300 percent (weight/volume) of the saturation solubilityof y-crystals of monosodium citrate at that tempe rature.

4. A process for crystallization of monosodium citrate monohydrateaccording to claim 2, wherein, when the aqueous solution contains bothmonosodium citrate and monosodium isocitrate, the crystallizationvelocity of monosodium citrate (g/L-l-lr) is controlled below maximumallowable crystallization velocity Y as determined from the equation Y219,000xin which X is the concentration of monosodium isocitrate in thesolution.

* I t =l=

1. PRISM-SHAPED CRYSTALS OF MONOSODIUM CITRATE MONOHYDRATE WHICH HAVETHE FOLLOWING X-RAY DIFFRACTION CHARACTERISTICS AT A=1.542 USING ACUK-LINE, 40 KV, 80 MA AND NI-FILTER: SPACING D (A) RELATIVE INTENSITIESSP @ 7.8 STRONG 6.4 MEDIUM 5.4 MEDIUM 4.1 WEAK 4.0 WEAK 3.89 VERY STRONG3.79 VERY WEAK 3.71 MEDIUM 3.58 WEAK 3.49 MEDIUM 3.35 WEAK 3.30 WEAK3.25 VERY WEAK 3.18 MEDIUM 2.92 WEAK 2.77 VERY WEAK 2.70 WEAK 2.60 WEAK2.55 WEAK 2.45 VERY WEAK 2.42 MEDIUM 2.36 VERY WEAK 2.34 WEAK 2.29 WEAK.2. A process for crystallization of monosodium citrate monohydrate whichcomprises subjecting to evaporation an aqueous solution containingmonosodium citrate whilst maintaining said solution at a temperaturebetween 20* and 60* centigrade and at a concentration of monosodiumcitrate of not less than 155 percent (weight/volume) of the saturationsolubility of gamma -crystals of monosodium citrate at that temperature.3. A process for crystallization of monosodium citrate monohydrateaccording to claim 2, wherein the concentration of monosodium citrate isnot over than 300 percent (weight/volume) of the saturation solubilityof gamma -crystals of monosodium citrate at that temperature.
 4. Aprocess for crystallization of monosodium citrate monohydrate accordingto claim 2, wherein, when the aqueous solution contains both monosodiumcitrate and monosodium (+) isocitrate, the crystallization velocity ofmonosodium citrate (g/l.- Hr) is controlled below maximum allowablecrystallization velocity Y as determined from the equation Y 219,000X1.53 in which X is the concentration of monosodium (+) isocitrate in thesolution.